RNA editing plays critical roles in cancer development, and multiple editing events collectively exert greater effects than individual events. However, the coordinated impact of RNA editing remains poorly understood. A comprehensive framework was proposed to investigate interactions among RNA editing events, capturing both the global editing landscape and site-specific functional effects. The resulting RNA editing modules were further explored to reveal gene interactions and regulatory mechanisms from the perspective of RNA editing. Using non-small cell lung cancer as an example, we identified more than 12 modules involved in immune regulation and metastasis-related processes, demonstrating their clinical relevance. Mechanistically, RNA editing influenced miRNA-mediated regulation of EIF2AK2 and PRKAR2A , transcription factor activity of AHR, and RNA-binding regulation of DDX3X, highlighting its role in shaping gene regulatory networks. Collectively, this study provides a systematic, module-based framework for understanding coordinated RNA editing, offering new insights into RNA editing–mediated gene interactions and revealing a complementary approach to study molecular mechanisms of diseases.
Zhang et al. (Wed,) studied this question.